This project aims to improve our understanding of what regulates T cell development in the thymus. Hence, it will have ramifications for our understanding and possible treatment of immuno-pathology in humans and in animals of agricultural importance. In particular, the thymus gives rise to two types of T cell: Alphabeta T cell receptor-bearing, and gammadelta T cell receptor- bearing. Molecular analyses of defined thymic progenitors will be used to ascertain when progenitor cells lose the potential to make both cell types, i.e. become committed to making one type or the other. These studies will be focused on testing a new working model for thymocyte development that we have been able to create based on our recent progress using normal and mutant mice that we have developed. Moreover, we shall continue to develop novel mouse mutants that are proving powerful in providing mechanistic insight into T cell development.